title: Cell penetrating peptide conjugated polymeric micelles as a high performance versatile nonviral gene carrier.
abstract: The major goal of this study is to design, synthesize, and evaluate linoleic acid and penetratin dual-functionalized chitosan (CS-Lin-Pen) as a nonviral gene carrier. The amphiphilic CS-Lin-Pen self-assembles to form cationic micelles in an aqueous environment. These polymeric micelles exhibited excellent hemocompatibility and cell viability, as evaluated by in vitro hemolysis and MTT assay, respectively. When CS-Lin-Pen micelles were added to plasmid DNA (pDNA) solution, the electrostatic interaction between the cationic micelles and anionic pDNA led to the formation of stable CS-Lin-Pen/pDNA polyplexes with ~100 nm in size. The resultant polyplexes demonstrated ~5-fold higher cellular uptake as compared to unmodified chitosan. Furthermore, CS-Lin-Pen micelles showed efficient protection of pDNA from DNase I attack and exhibited ~34-40-fold higher transfection in comparison with unmodified chitosan in HEK 293, CHO, and HeLa cells. These findings illustrate that the CS-Lin-Pen micelles could be exploited as a potential nonviral vector for efficient gene therapy.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nursing, and Allied Sciences, North Dakota State University , Fargo, North Dakota 58105, United States.
authors.forename: Buddhadev
authors.initials: B
authors.lastname: Layek
authors.forename: Jagdish
authors.initials: J
authors.lastname: Singh
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016466:CHO Cells; D002236:Carbohydrate Conformation; D002470:Cell Survival; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D003412:Cricetulus; D004247:DNA / Q000235:genetics; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D019787:Linoleic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008823:Micelles; D008969:Molecular Sequence Data; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D057846:Cell-Penetrating Peptides; D008823:Micelles; D011108:Polymers; D004247:DNA; D048271:Chitosan; D019787:Linoleic Acid